Many vessels in animals transport fluids from one body location to another. Frequently, fluid flows in a substantially unidirectional manner along the length of the vessel. Native valves within the heart and veins function to regulate blood flow within the body. Heart valves positioned within the heart direct the flow of blood to and from other organs and pump oxygenated blood to the rest of the body. Venous valves are typically bicuspid valves positioned at varying intervals within veins to permit substantially unidirectional blood to flow toward the heart. Body vessels such as veins transport blood to the heart and arteries carry blood away from the heart. Occasionally, congenital defects or injury to valves within a body vessel can result in an undesirable amount of retrograde fluid flow across a valve therein, and compromise the unidirectional flow of fluid across the valve.
Various implantable medical devices are advantageously inserted within various portions of the body. Minimally invasive techniques and instruments for placement of intraluminal medical devices have been developed to treat and repair undesirable conditions within body vessels, including treatment of conditions that affect blood flow such as venous valve insufficiency. Various percutaneous methods of implanting medical devices within the body using intraluminal transcatheter delivery systems can be used to treat a variety of conditions. One or more intraluminal medical devices can be introduced to a point of treatment within a body vessel using a delivery catheter device passed through the vasculature communicating between a remote introductory location and the implantation site, and released from the delivery catheter device at the point of treatment within the body vessel. Intraluminal medical devices can be deployed in a body vessel at a point of treatment and the delivery device subsequently withdrawn from the vessel, while the medical device retained within the vessel to provide sustained improvement in valve function or to increase vessel patency. For example, an implanted medical device can improve the function of native valves by blocking or reducing retrograde fluid flow. Alternatively, a prosthetic valve can be implanted to replace the function of damaged or absent native valves within the body.
One challenge for development of a prosthetic valve with the venous system is mitigating thrombus formation that can occlude the vessel and/or lead to loss of functionality of the valve structures that regulate blood flow. In contrast to the arterial system, the lower flow rates in some body vessels such as the deep veins of the legs and feet can lead to stagnation of blood in the pockets about the bases of the leaflets or valve structure due to the inability of the blood to be flushed and refreshed thereabout. The pockets can fill with thrombus that compromises the ability the leaflets or valve structure to open and close in response to antegrade and retrograde flow (i.e., pressure differentials across the valve). For example, fibrinogen absorbed on to the surface of an implanted prosthetic valve can form a layer that triggers the biochemical pathway leading fibrin deposition, platelet aggregation, and thrombus formation.
Remodelable materials, such as extracellular matrices (ECM), can be used to provide a thrombo-resistant surface in an implantable prosthetic valve. Prosthetic valves desirably include valve leaflets formed from a remodelable material such that, upon implantation, the remodelable material can be used to form a permanently non-thrombogenic leaflet surface. Small intestinal submucosa (SIS) is a commercially available ECM material (Cook Biotech Inc., West Lafayette, Ind.) derived from a porcine source and processed to retain remodelability.
When implanted in some vessels such as veins, however, remodelable material is often subjected to intermittent fluid flow with intervals of blood stagnation. Changes in the flow rate, flow direction or fluid pressure of intraluminal fluid across an implanted remodelable material have the potential to disrupt or slow the remodeling process. The intraluminal fluid flow can be characterized by parameters such as pressure, direction, composition and flow rate across the interface. Intraluminal fluid flow in a vascular environment is subject to regular modulations in pressure and fluid flow due to respiratory and calf muscle function. The remodeling process itself may be linked to the flow of fluid across the remodelable surface. Recent investigations have shown that SIS-based remodeling of implanted medical devices can occur by recruitment of cells directly from intraluminal circulation. See Brountzos, et al, “Remodeling of suspended small intestinal submucosa venous valve: an experimental study in sheep to assess the host cells' origin,” J. Vasc. Interv. Radiol., 14(3), 349-356 (March 2003).
While the ability of valve leaflets made of ECM materials to remodel has been demonstrated clinically, the surface of the newly-implanted ECM materials such as SIS can be vulnerable to thrombus formation, particularly in sinus regions near valves. Because remodeling is a process that can take days, weeks or longer, depending on the environment, thrombogenicity has remained a clinical issue to be addressed when using remodelable biomaterials. In particular, implantable valves having valve leaflets comprising a remodelable material may thicken or undergo thrombotic deposition during the remodeling period within the body vessel. This may be the result of progressive fibrin deposition due to hemodynamics of blood flow contacting a portion of the valve leaflet near the wall of the body vessel. For example, blood may stagnate in the sinus defined by a valve leaflet and an adjacent portion of the body vessel wall. As a result, during remodeling of the valve leaflet after implantation, the thickness of the valve leaflet may increase on the upstream side of the valve leaflet upon endothelialization and the downstream side of the leaflet may sustain fibrin deposition and progressive thrombogenic deposition without significant endothelialization. The resulting thickening of the valve leaflet and/or fibrotic deposition thereon may reduce or compromise valve function of the remodeled valve leaflet within a period of about 3-6 weeks.
What is needed are prosthetic valves that provide for remodeling of at least a portion of the valve while reducing exposure of the remodelable material to conditions that may undesirably permit or promote the deposition of thrombogenic material on the remodelable material or thickening of the valve leaflet during remodeling. A prosthetic valve configured to permit contact of a remodelable valve leaflet with blood or tissue that promotes remodeling for a time period effective for remodeling prior to configuring the valve leaflet as an operable configuration to regulate fluid flow would be particularly desirable.